Osmotic delivery device comprising an insulinotropic peptide and uses thereof

Abstract

A suspension formulation of an insulinotropic peptide (e.g., glucagon-like peptide-1 (GLP-1) or exenatide) is described. The suspension formulation comprises (i) a non-aqueous, single-phase vehicle, comprising one or more polymer and one or more one solvent, wherein the vehicle exhibits viscous fluid characteristics, and (ii) a particle formulation comprising the insulinotropic peptide, wherein the peptide is dispersed in the vehicle. The particle formulation further includes a stabilizing component comprising one or more stabilizers, for example, carbohydrates, antioxidants, amino acids, and buffers. Devices for delivering the suspension formulations and methods of use are also described.

1 . A suspension formulation suitable for use in a delivery device, the suspension formulation comprising:
 a particle formulation comprising:
 an insulinotropic peptide; 
 a carbohydrate; 
 an antioxidant; and 
 a buffer; and 
   a non-aqueous, single-phase suspension vehicle that consists essentially of about 20 wt % to about 60 wt % solvent and about 80 wt % to about 40 wt % pyrrolidone, wherein:
 the solvent is at least one of lauryl lactate, lauryl alcohol, and benzyl benzoate 
 the suspension vehicle exhibits viscous fluid characteristics; and 
 the particle formulation is dispersed in the vehicle. 
   
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The suspension formulation of  claim 1 , wherein the insulinotropic peptide is at least one of exenatide, a derivative of exenatide, and an analogue of exenatide. 
     
     
         5 . (canceled) 
     
     
         6 . The suspension formulation of  claim 1 , wherein the buffer is selected from at least one of citrate, histidine, succinate, and tris. 
     
     
         7 . (canceled) 
     
     
         8 . The suspension formulation of  claim 1 , wherein the carbohydrate is at least one of lactose, sucrose, trehalose, cellobiose, and raffinose. 
     
     
         9 . (canceled) 
     
     
         10 . The suspension formulation of  claim 1 , wherein the solvent is benzyl benzoate. 
     
     
         11 . (canceled) 
     
     
         12 . The suspension formulation of  claim 1 , wherein the pyrrolidone is polyvinylpyrrolidone. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . A delivery device comprising the suspension formulation of  claim 1 . 
     
     
         17 . A method of treating type II diabetes in a subject in need of such treatment, the method comprising:
 delivering the suspension formulation of  claim 1  from a delivery device at a substantially uniform rate for a period of about one month to about one year.   
     
     
         18 . The method of  claim 17 , wherein the period is about three months to about one year. 
     
     
         19 . The method of  claim 17 , wherein the delivering the suspension formulation is at a dose of 20 μg/day of the insulinotropic peptide. 
     
     
         20 . A method of manufacturing a delivery device, the method comprising:
 loading the suspension formulation of  claim 1  into a reservoir of the delivery device.   
     
     
         21 - 35 . (canceled) 
     
     
         36 . The suspension formulation of  claim 1 , wherein the suspension vehicle has a viscosity of about 5,000 poise to about 50,000 poise at 37° C. 
     
     
         37 . The suspension formulation of  claim 1 , wherein the antioxidant is methionine. 
     
     
         38 . The suspension formulation of  claim 1 , wherein each particle of the particle formulation has a diameter of about 3 μm to about 50 μm. 
     
     
         39 . The suspension formulation of  claim 1 , wherein the particle formulation is chemically and physically stable for at least one month to at least one year at a delivery temperature of about 37° C. to about 40° C. 
     
     
         40 . The suspension formulation of  claim 1 , wherein the particle formulation is chemically and physically stable for at least three months to at least two years at a storage temperature of about 5° C. to about 25° C. 
     
     
         41 . A method of manufacturing the suspension formulation of  claim 1 , the method comprising:
 forming particles of the particle formulation using at least one of spray drying and lyophilization, such that the particles are substantially uniform in shape and size.   
     
     
         42 . The delivery device of  claim 16 , wherein the delivery device delivers the suspension formulation at least one of osmotically, mechanically, electromechanically, and chemically. 
     
     
         43 . The delivery device of  claim 16 , wherein the delivery device has a delivery orifice with a first diameter of about 100 μm to about 500 μm, and each particle of the particle formulation has a second diameter of about 3 μm to about 50 μm. 
     
     
         44 . The delivery device of  claim 16 , wherein the delivery device has a reservoir for receiving the suspension formulation, the reservoir having a volume less than or equal to 100 μl.